Global developmental delay and intellectual disability in the era of genomics: Diagnosis and challenges in resource limited areas.

Aims: To report the diagnostic yield of clinical singleton whole exome sequencing (WES) performed among a group of Jordanian children presenting with global developmental delay /intellectual disability (GDD/ID), discuss the underlying identified genetic disorders and the challenges encountered.

Patients And Methods: This retrospective medical record review study included 154 children who were diagnosed with GDD/ID at our clinic at Jordan University Hospital between 2016 and 2021, and whose diagnostic work up included WES.

Results: Consanguinity among parents was reported in 94/154 (61.

INTS13 variants causing a recessive developmental ciliopathy disrupt assembly of the Integrator complex.

Oral-facial-digital (OFD) syndromes are a heterogeneous group of congenital disorders characterized by malformations of the face and oral cavity, and digit anomalies. Mutations within 12 cilia-related genes have been identified that cause several types of OFD, suggesting that OFDs constitute a subgroup of developmental ciliopathies. Through homozygosity mapping and exome sequencing of two families with variable OFD type 2, we identified distinct germline variants in INTS13, a subunit of the Integrator complex.

Generation of three human induced pluripotent stem cell lines with IRX5 knockout and knockin genetic editions using CRISPR-Cas9 system.

Studies on animal models have shown that Irx5 is an important regulator of cardiac development and that it regulates ventricular electrical repolarization gradient in the adult heart. Mutations in IRX5 have also been linked in humans to cardiac conduction defects. In order to fully characterize the role of IRX5 during cardiac development and in cardiomyocyte function, we generated three genetically-modified human induced pluripotent stem cell lines: two knockout lines (heterozygous and homozygous) and a knockin HA-tagged line (homozygous).

Evaluation of treatment of acne scars with 25% trichloroacetic acid chemical peel followed by manual dermasanding.

Background: Acne scars are common problems encountered in daily dermatologic practice.

Aims: To evaluate the effectiveness and safety of 25% trichloroacetic acid (TCA) alone or followed by manual dermasanding in repeated sessions for the treatment of mild and moderate acne scars.

Patients/methods: Thirteen patients (nine females and four males) were enrolled.

Human model of IRX5 mutations reveals key role for this transcription factor in ventricular conduction.

Aims: Several inherited arrhythmic diseases have been linked to single gene mutations in cardiac ion channels and interacting proteins. However, the mechanisms underlying most arrhythmias, are thought to involve altered regulation of the expression of multiple effectors. In this study, we aimed to examine the role of a transcription factor (TF) belonging to the Iroquois homeobox family, IRX5, in cardiac electrical function.

Congenital insensitivity to pain with anhidrosis syndrome: A series from Jordan.

Objectives: To present the clinical picture, the associated complications and the genetic findings of Jordanian patients diagnosed with Congenital insensitivity to pain with anhidrosis (CIPA).

Patients And Methods: This is a retrospective study including 7 patients diagnosed with CIPA presenting to Jordan University Hospital neurology clinic between 2001 and 2017.

Results: Among five families, seven patients were diagnose with CIPA and followed for a period ranging from one month to 6 years.

Biallelic loss of function variants in PPP1R21 cause a neurodevelopmental syndrome with impaired endocytic function.

Next-generation sequencing (NGS) has been instrumental in solving the genetic basis of rare inherited diseases, especially neurodevelopmental syndromes. However, functional workup is essential for precise phenotype definition and to understand the underlying disease mechanisms. Using whole exome (WES) and whole genome sequencing (WGS) in four independent families with hypotonia, neurodevelopmental delay, facial dysmorphism, loss of white matter, and thinning of the corpus callosum, we identified four previously unreported homozygous truncating PPP1R21 alleles: c.

Estimating the birth prevalence and pregnancy outcomes of congenital malformations worldwide.

Congenital anomaly registries have two main surveillance aims: firstly to define baseline epidemiology of important congenital anomalies to facilitate programme, policy and resource planning, and secondly to identify clusters of cases and any other epidemiological changes that could give early warning of environmental or infectious hazards. However, setting up a sustainable registry and surveillance system is resource-intensive requiring national infrastructure for recording all cases and diagnostic facilities to identify those malformations that that are not externally visible. Consequently, not all countries have yet established robust surveillance systems.

Rare single gene disorders: estimating baseline prevalence and outcomes worldwide.

As child mortality rates overall are decreasing, non-communicable conditions, such as genetic disorders, constitute an increasing proportion of child mortality, morbidity and disability. To date, policy and public health programmes have focused on common genetic disorders. Rare single gene disorders are an important source of morbidity and premature mortality for affected families.

Biallelic variants in KIF14 cause intellectual disability with microcephaly.

Kinesin proteins are critical for various cellular functions such as intracellular transport and cell division, and many members of the family have been linked to monogenic disorders and cancer. We report eight individuals with intellectual disability and microcephaly from four unrelated families with parental consanguinity. In the affected individuals of each family, homozygosity for likely pathogenic variants in KIF14 were detected; two loss-of-function (p.

ASSESSMENT OF KNOWLEDGE, ATTITUDE AND PRACTICE TOWARDS CONSANGUINEOUS MARRIAGES AMONG A COHORT OF MULTIETHNIC HEALTH CARE PROVIDERS IN SAUDI ARABIA.

This study aimed to assess knowledge, attitude and practice related to consanguinity among multiethnic health care providers in the Kingdom of Saudi Arabia. Using a cross-sectional study design, a validated, self-administered close-ended questionnaire was randomly distributed to health care providers in different health institutions in the country between 1st August 2012 and 31st July 2013. A total of 1235 health care providers completed the study questionnaire.

E-learning for research capacity strengthening in sexual and reproductive health: the experience of the Geneva Foundation for Medical Education and Research and the Department of Reproductive Health and Research, World Health Organization.

Unlabelled: Technological advancement has resulted in the increasing use of e-learning and online education, initially in high-income countries and increasingly in low- and middle-income countries.

Background: In 2010, the Geneva Foundation for Medical Education and Research, in collaboration with the World Health Organization and partner institutions, developed an online postgraduate course "From Research to Practice: Training Course in Sexual and Reproductive Health Research". This course takes advantage of the advancing Internet technology to provide training opportunities to health professionals mostly from low- and middle-income countries whose access to quality education is constrained by time, financial resources, or both.

Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy.

Early-onset epileptic encephalopathy (EOEE) represents a heterogeneous group of severe disorders characterized by seizures, interictal epileptiform activity with a disorganized electroencephalography background, developmental regression or retardation, and onset before 1 year of age. Among a cohort of 57 individuals with epileptic encephalopathy, we ascertained two unrelated affected individuals with EOEE associated with developmental impairment and autosomal-recessive variants in AP3B2 by means of whole-exome sequencing. The targeted sequencing of AP3B2 in 86 unrelated individuals with EOEE led to the identification of an additional family.

Loss of Iroquois homeobox transcription factors 3 and 5 in osteoblasts disrupts cranial mineralization.

Cranial malformations are a significant cause of perinatal morbidity and mortality. Iroquois homeobox transcription factors (IRX) are expressed early in bone tissue formation and facilitate patterning and mineralization of the skeleton. Mice lacking Irx5 appear grossly normal, suggesting that redundancy within the Iroquois family.

Exome sequencing discloses KALRN homozygous variant as likely cause of intellectual disability and short stature in a consanguineous pedigree.

Background: The recent availability of whole-exome sequencing has opened new possibilities for the evaluation of individuals with genetically undiagnosed intellectual disability.

Results: We report two affected siblings, offspring of first-cousin parents, with intellectual disability, hypotonia, short stature, growth hormone deficiency, and delayed bone age. All members of the nuclear family were genotyped, and exome sequencing was performed in one of the affected individuals.

Experience of a multidisciplinary task force with exome sequencing for Mendelian disorders.

Background: In order to optimally integrate the use of high-throughput sequencing (HTS) as a tool in clinical diagnostics of likely monogenic disorders, we have created a multidisciplinary "Genome Clinic Task Force" at the University Hospitals of Geneva, which is composed of clinical and molecular geneticists, bioinformaticians, technicians, bioethicists, and a coordinator.

Methods And Results: We have implemented whole exome sequencing (WES) with subsequent targeted bioinformatics analysis of gene lists for specific disorders. Clinical cases of heterogeneous Mendelian disorders that could potentially benefit from HTS are presented and discussed during the sessions of the task force.

Pathogenic Variants in PIGG Cause Intellectual Disability with Seizures and Hypotonia.

Glycosylphosphatidylinositol (GPI) is a glycolipid that anchors >150 various proteins to the cell surface. At least 27 genes are involved in biosynthesis and transport of GPI-anchored proteins (GPI-APs). To date, mutations in 13 of these genes are known to cause inherited GPI deficiencies (IGDs), and all are inherited as recessive traits.

Familial epilepsy in Algeria: Clinical features and inheritance profiles.

Purpose: To document the clinical characteristics and inheritance pattern of epilepsy in multigeneration Algerian families.

Methods: Affected members from extended families with familial epilepsy were assessed at the University Hospital of Oran in Algeria. Available medical records, neurological examination, electroencephalography and imaging data were reviewed.

Maternal Iron Status in Pregnancy and Long-Term Health Outcomes in the Offspring.

Iron is an essential micronutrient and is important not only in carrying oxygen but also to the catalytic activity of a variety of enzymes. In the fetus, it is vital to the synthesis of hemoglobin and in brain development. Iron deficiency (ID) anemia in pregnancy is a common problem, even in high-income country settings.

Exome sequencing reveals pathogenic mutations in 91 strains of mice with Mendelian disorders.

Spontaneously arising mouse mutations have served as the foundation for understanding gene function for more than 100 years. We have used exome sequencing in an effort to identify the causative mutations for 172 distinct, spontaneously arising mouse models of Mendelian disorders, including a broad range of clinically relevant phenotypes. To analyze the resulting data, we developed an analytics pipeline that is optimized for mouse exome data and a variation database that allows for reproducible, user-defined data mining as well as nomination of mutation candidates through knowledge-based integration of sample and variant data.

Triple A syndrome with a novel indel mutation in the AAAS gene and delayed puberty.

Triple A syndrome, formerly known as Allgrove syndrome, is an autosomal recessive disorder characterized clinically by adrenal insufficiency, alacrima, achalasia, and neurological abnormalities. We report a 17-year-old boy presented to the endocrine clinic with delayed puberty and a 4-year's history of fatigue and muscle weakness. He had achalasia, alacrima, and skin and mucosal hyperpigmentation.

Premarital screening for hemoglobinopathies: experience of a single center in Kurdistan, Iraq.

Background: A program for the prevention of major hemoglobinopathies was initiated in 2008 in the Kurdistan region of Iraq. This study reports on the achievements and challenges of the program.

Methods: A total of 102,554 individuals (51,277 couples) visiting a premarital center between 2008 and 2012 were screened for carrier status of hemoglobinopathies, and at-risk couples were counseled.